Yin E, Uchiyama M, Niimi M
Department of Surgery, Teikyo University, Tokyo, Japan; Department of Cardiovascular Surgery, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Surgery, Teikyo University, Tokyo, Japan.
Transplant Proc. 2018 Jan-Feb;50(1):274-282. doi: 10.1016/j.transproceed.2017.12.021.
Shigyakusan (also known as Tsumura Japan [TJ]-35) is composed of peony, bitter orange, licorice, and Bupleuri radix is used for cholecystitis and gastritis as an anti-inflammatory agent. We investigated the effect of TJ-35 on alloimmune response in a murine heart transplantation model. CBA mice that underwent transplantation of a C57BL/6 (B6) heart were assigned to four groups: no treatment, TJ-35-exposed, each component-exposed, or each component missing-exposed. The four groups above each received oral administration of TJ-35, each component, or TJ-35 with each component missing from the day of transplantation until 7 days, respectively. Untreated CBA recipients rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). TJ-35-exposed CBA recipients had significantly prolonged B6 allograft survival (MST, 20.5 days). However, MSTs of CBA recipients that had been administered each component and TJ-35 with each component missing did not reach that of TJ-35-exposed recipients. Adoptive transfer of CD4 splenocytes from TJ-35-exposed primary allograft recipients resulted in significant prolonged allograft survival in naïve secondary recipients (MST, 63 days). Flow cytometry studies showed that the percentage of CD4CD25Foxp3 cell population was increased in TJ-35-exposed CBA recipients. In conclusion, TJ-35-induced prolongation of fully allogeneic cardiac allografts and may generate regulatory CD4CD25Foxp3 cells in our model. The effect seemed to require all components of TJ-35.
柴朴汤（也称为日本津村[TJ]-35）由芍药、枳实、甘草和柴胡组成，作为抗炎剂用于胆囊炎和胃炎。我们在小鼠心脏移植模型中研究了TJ-35对同种免疫反应的影响。接受C57BL/6（B6）心脏移植的CBA小鼠被分为四组：不治疗组、TJ-35暴露组、各成分暴露组或各成分缺失暴露组。上述四组分别从移植当天至第7天接受TJ-35、各成分或缺失各成分的TJ-35的口服给药。未治疗的CBA受体急性排斥B6心脏移植物（中位生存时间[MST]，7天）。TJ-35暴露的CBA受体的B6同种异体移植物存活时间显著延长（MST，20.5天）。然而，给予各成分以及缺失各成分的TJ-35的CBA受体的MST未达到TJ-35暴露受体的MST。将TJ-35暴露的原发性同种异体移植物受体的CD4脾细胞过继转移至未致敏的继发性受体中，导致同种异体移植物存活时间显著延长（MST，63天）。流式细胞术研究表明，TJ-35暴露的CBA受体中CD4CD25Foxp3细胞群体的百分比增加。总之，在我们的模型中，TJ-35可诱导完全异基因心脏同种异体移植物存活时间延长，并可能产生调节性CD4CD25Foxp3细胞。这种作用似乎需要TJ-35的所有成分。
